Competition for iron plays an important role in host-bacterial interaction. High affinity iron binding proteins in host body fluids severly limit the availability of iron for microbial growth, and microorganisms must be able to compete for this iron if an infection is to be established. In this project, the mechanism of iron transport and the role in virulence of Shigella will be studied. Iron transport compounds (siderophores) produced by these enteric pathogens will be isolated and the ability of these compounds to compete with host proteins for iron will be determined. The role of iron transport in virulence of Shigella can be assessed by isolating mutants defective in iron transport and comparing their virulence with that of wild type Shigella in experimental animals. Additional studies will focus on the genetic and biochemical basis of "iron responsive" mutants of Shigella. These mutants are normally avirulent, but virulence is enhanced by injection of iron into the host. These mutants can be distinguished from wild type Shigella by their inability to bind the dye Congo red from agar media. The cell component responsible for dye binding will be isolated and characterized to determine its possible role in virulence. Genetic studies will primarily be concerned with the involvement of phage or plasmids in virulence of Shigella.